Benign and Malignant Thyroid Disease Among Those Exposed as Children to Fallout from the Chornobyl Accident Studies of populations exposed to fallout from nuclear tests or accidents are a major focus of this project. The Chernobyl nuclear reactor accident in Ukraine in 1986 has led to an unprecedented increase in thyroid cancer among children in Belarus, northwestern Ukraine, and bordering Russian provinces. In a case-control study of thyroid cancer in Belarus, with individual dose estimates, a statistically significant dose-specific link between thyroid cancer and radiation dose from fallout related to the Chornobyl accident was demonstrated. With the assistance of the Department of Energy (DOE) and the Nuclear Regulatory Commission (NRC), NCI has organized long-term follow-up studies of benign and malignant thyroid disease among those exposed as children to fallout from the Chornobyl accident in Belarus and in Ukraine. To date, the thyroid glands of approximately 12,000 subjects in each country have been screened biennially. A prevalence analysis based on data from the first screening is underway. Cancer Mortality Among the Population Exposed to Radioactive Waste Dumped in the Techa River Adjacent to the Mayak Nuclear Facility in Russia Villagers living along the banks of the Techa River in Russia were exposed to chronic external and internal radiation from the Mayak nuclear facility. Cancer mortality is being evaluated in a cohort of approximately 26,000 people who received large doses of radiation from the radioactive waste dumped into the river. Current efforts focus on improving data quality, tracing the population for vital status information, and on statistical analyses. Thyroid Nodules as a Measure of Radiation Risk Among a Population of 3000 Residents in Kazakhstan Exposed as Children to Fallout from Nuclear Testing at the Semipalatinsk Test Site Thyroid nodule prevalence, ascertained by ultrasound screening, was used as a biomarker for radiation-related risk in a population of 3000 childhood residents of villages in Kazakhstan affected by radioactive fallout from nuclear bomb tests at the nearby Semipalatinsk Test Site. An ongoing dose reconstruction, based on Russian models for fallout deposition, archival and interview data on residence at the time of fallout events, source and consumption of milk and milk products, and models for iodine transport from pasture to food, yielded individual estimates of thyroid dose from external and internal radiation sources. Preliminary estimates of dose response for nodule prevalence suggest that the relative biological effectiveness of radiation from ingested 131-I compared to gamma rays from external sources is about 65% and is unlikely to be less than 25%. Lung Cancer and High Levels of Indoor Radon in China A comprehensive case-control study of lung cancer in rural China provided evidence that high levels of indoor radon increased lung cancer risk and supported findings from meta-analyses of indoor studies and from miners. This study is being pooled with data from another large case-control study of lung cancer and radon conducted in a more urban area of China to refine the risk estimates. A measurement sub-study conducted over a three-year period found that temporal variation in radon levels represented the greatest source of uncertainty in radon measurements. Adjusting for this uncertainty in measurement increased the excess risk estimates of lung cancer by 50-100%. This suggests that radon studies using similar dosimetry may underestimate radon effects. Ultraviolet Sunlight Exposure, Ionizing Radiation, and Risk of Melanoma and Non Melanoma Skin Cancer Exposure to ultraviolet (UV) frequency exposure from sunlight plays a key role in occurrence of melanoma and non-melanoma skin cancer (NMSC), but the nature of the relationship is complex and not fully understood. It has recently been suggested that melanoma and basal cell carcinoma (BCC) may be caused by intense, intermittent UV exposure from the sun, particularly during childhood. There also is evidence that recent sun exposure may affect the risk of all three major types of skin cancer: squamous cell carcinoma (SCC), BCC and melanoma. The well-known carcinogenic effect of ionizing radiation (IR) has been associated primarily with BCC. In an investigation of cancer risks in a large cohort of US radiologic technologists (USRT), REB investigators found (a) a significant effect of IR exposure (using proxy measures) on risk of BCC and melanoma; and (b) an increased risk of all three types of skin cancer associated with a proxy measure for residential UV exposure history. Over 2,000 NMSC cases have been identified among the USRT cohort based on questionnaire data through 1994-98; by the end of 2003, an estimated total of 8,000 incident NMSC and 500 incident melanoma cases will have arisen within the USRT cohort. The occurrence of a large number of incident skin cancer cases within the USRT provides an excellent opportunity for studying (a) the interaction between the two carcinogens (UV and IR), with well characterized cellular damage at the DNA level, and (b) interaction between UV/IR exposure and genetic factors. In preparation for a new case-cohort study of 5,000+ incident NMSC and 350 cutaneous melanoma cases to be spearheaded by investigators in REB and GEB, three pilot studies are currently being conducted. First, REB investigators are collaborating with an investigator from Dartmouth Medical School to identify which questions on sun exposure from the investigator's recent, large case-control study in New Hampshire most strongly predict pre-cancerous skin damage changes based on histopathological review of the level of actinic damage in skin surrounding NMSC tumors from the New Hampshire cases. Second, REB investigators are collaborating with a Harvard School of Public Health co-investigator from the New Hampshire study to assess the role of certain genetic variants of the XRCC1 DNA repair gene and related haplotypes in risk of NMSC prior to undertaking a large-scale study of these variants and haplotypes. Third, REB investigators are conducting a daily diary study of 30 radiologic technologists to ascertain the types and sources of recreational sun exposure prior to developing a questionnaire for the proposed case-cohort study.